Cellular neuroscienceStatus epilepticus induces a TrkB to p75 neurotrophin receptor switch and increases brain-derived neurotrophic factor interaction with p75 neurotrophin receptor: An initial event in neuronal injury induction
Section snippets
Animals and induction of SE
Adult male Wistar rats (Instituto Ferreyra, Córdoba, Argentina) aged 2–2.5 months and weighing 250–320 g were used and housed under environmentally controlled conditions. Animals received water and food ad libitum, and were maintained in a 12-h light/dark cycle. The experimental protocol for this study followed the guidelines of the USA National Research Council Guide for the Care and Use of Laboratory Animals (National Research Council, 1996) and was approved by the Animal Care and Use
SE decreases TrkB and increase p75ntr protein levels
In order to make inferences on the possible roles of BDNF in vivo after CNS injury, it is necessary to determine the possible modifications of the whole BDNF signaling system (TrkB, p75ntr, sortilin, mature BDNF and proBDNF). Systemic administration of pilocarpine leads to SE, characterized by intense seizures of a sustained nature, typically starting with violent, generalized clonic–tonic seizures. Animals were allowed to remain in this condition for 3 h, exhibiting continuous myoclonus of
Discussion
Since the discovery that neurotrophins (NT) can regulate not only neuronal survival and differentiation but also neuronal apoptosis (Barret and Bartlet 1994, Frade et al 1996, Frade et al 1997), many questions have arisen regarding how such opposite functions can be regulated by the same signaling protein. In the present study we show that SE induces a switch between TrkB and p75ntr receptor levels, forcing BDNF to interact largely with one receptor rather than the other, an event that might
Acknowledgments
This work was supported by grants from CONICET, FONCYT (PICT 5-14398) and SECyT-UNC. D.H.M. is a career member of CONICET; N.U. and A.A. are recipients of doctoral fellowships from CONICET. We thank Laura Montroull for her help with some experiments.
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Beyond good and evil: A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment
2018, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Since antidepressants can modulate neuronal activity, they may also subjugate the balance of mBDNF/proBDNF and/or mBDNF/propeptide to promote more efficient neuronal networking, thus favoring neuroplasticity on demand. It is worth noting that detrimental stimuli, such as status epilepticus, can also change the balance of hippocampal TrkB/p75R signaling by switching TrkB towards p75R expression and then favoring either mBDNF or proBDNF receptor binding (Unsain et al., 2008). In this scenario, the antidepressants become a type of “organizer”, by allowing the (re) balance between TrkB and p75R signaling, by amplifying neuroplastic possibilities toward fine-tuning of neuronal networking on demand of contingencies and specific requirements.
Seizing Control of KCC2: A New Therapeutic Target for Epilepsy
2017, Trends in NeurosciencesCalpain-dependent truncated form of TrkB-FL increases in neurodegenerative processes
2016, Molecular and Cellular NeuroscienceCitation Excerpt :The cleavage products of calpains action on their substrate may show biological activity (Ma, 2013). One of the most distinctive features of SE is that it induces an increase in the levels of BDNF and proBDNF, as well as an imbalance in the expression of their receptors, TrkB and p75ntr, respectively, before the onset of neuronal death, a feature shared with other neurodegenerative diseases (Unsain et al., 2008, 2009; Brito et al., 2013). In this regard, it has been demonstrated in models of ischemia, Alzheimer disease (AD) and SE, that calpain can process TrkB full-length (TrkB-FL), producing a cleaved receptor, the truncated TrkB-FL (Tc TrkB-FL), which is similar to the splice-variant TrkB T1 in that both receptors lack most of the intracellular domain.
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Present address: Natural Sciences Department, Hostos Community College, City University of New York.